Repeat Expansion Detection with ExpansionHunter

Short tandem repeats (STRs) are regions of the genome consisting of repetitions of short DNA segments called repeat units. STRs can expand to lengths beyond the normal range and cause mutations called repeat expansions. Repeat expansions are responsible for many diseases, including Fragile X syndrome, amyotrophic lateral sclerosis, and Huntington's disease.

DRAGEN includes a repeat expansion detection method called ExpansionHunter. ExpansionHunter performs sequence-graph based realignment of reads that originate inside and around each target repeat. ExpansionHunter then genotypes the length of the repeat in each allele based on these graph alignments.

The ExpansionHunter is designed for PCR-free whole genome samples. Repeats are only genotyped if the coverage at the locus is at least 10x. The ExpansionHunter cannot be run on multiple FASTQ files that are assigned to different library IDs in the fastq_list.csv file.

More information and analysis are available in the following ExpansionHunter papers:

Dolzhenko et al., Detection of long repeat expansions from PCR-free whole-genome sequence data 2017
Dolzhenko et al., ExpansionHunter: A sequence-graph based tool to analyze variation in short tandem repeat regions 2019